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Purpose: The aim of this study was to compare toxicities, disease control, survival outcomes, and patterns of failure between groups of limited-stage small-cell lung cancer patients treated with once-daily versus twice-daily radiotherapy and concurrent chemotherapy.Materials and Methods: This single-institution retrospective analysis included a comparison of two of radiotherapy regimens to planned doses of (1) > or =59.4 Gy at 1.8-2.0 Gy per once-daily fraction or (2) > or =45 Gy at 1.5 Gy per twice-daily fractions with concurrent platinum-based chemotherapy. Comparative analyses of toxicities and disease control were performed.Results: A total of 71 patients were included in the present study (17 once-daily, 54 twice-daily). Patient, tumor, staging, and treatment factors were similar between the two treatment groups. Median planned radiotherapy doses were 60 Gy (range 59.4-70.0 Gy) and 45 Gy (range 45-51 Gy) for the once-daily and twice-daily groups, respectively. Acute toxicities were similar between the groups ( approximately 20% grade 3 esophagitis). At a median survival follow-up of 26.2 months (range 3.4-85.5 months), 42 patients had died. The 2-year overall survival estimates were similar at 43% and 49% for the once-daily versus twice-daily groups, respectively. Isolated in-field failures were similar between the two groups ( approximately 17%).Conclusion: The present analysis did not detect a statistically significant difference in acute toxicities, disease control, or survival outcomes in limited-stage small-cell lung cancer patients treated with concurrent chemotherapy and once-daily versus twice-daily radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The American College of Chest Physicians (ACCP) produced an evidence-based guideline on treatment of patients with small-cell lung cancer (SCLC). Because of the relevance of this guideline to American Society of Clinical Oncology (ASCO) membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations., Methods: The ACCP guideline on the treatment of SCLC was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel updated the literature search, reviewed the content, and considered additional recommendations., Results: The ASCO Endorsement Panel determined that the recommendations from the ACCP guideline, published in 2013, are clear, thorough, and based on current scientific evidence. ASCO endorses the ACCP guideline on the treatment of SCLC, with the addition of qualifying statements., Recommendations: Surgery is indicated for selected stage I SCLC. Limited-stage disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle one or two of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. Extensive-stage disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in patients with limited-stage disease who achieve a complete or partial response to initial therapy and may do so in similarly responding patients with extensive-stage disease as well. Additional information is available at http://www.asco.org/endorsements/sclc and http://www.asco.org/guidelineswiki., (© 2015 by American Society of Clinical Oncology.)

Background: Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases (N2) have shown the feasibility of resection after concurrent chemotherapy and radiotherapy with promising rates of survival. We therefore did this phase III trial to compare concurrent chemotherapy and radiotherapy followed by resection with standard concurrent chemotherapy and definitive radiotherapy without resection., Methods: Patients with stage T1-3pN2M0 non-small-cell lung cancer were randomly assigned in a 1:1 ratio to concurrent induction chemotherapy (two cycles of cisplatin [50 mg/m(2) on days 1, 8, 29, and 36] and etoposide [50 mg/m(2) on days 1-5 and 29-33]) plus radiotherapy (45 Gy) in multiple academic and community hospitals. If no progression, patients in group 1 underwent resection and those in group 2 continued radiotherapy uninterrupted up to 61 Gy. Two additional cycles of cisplatin and etoposide were given in both groups. The primary endpoint was overall survival (OS). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00002550., Findings: 202 patients (median age 59 years, range 31-77) were assigned to group 1 and 194 (61 years, 32-78) to group 2. Median OS was 23.6 months (IQR 9.0-not reached) in group 1 versus 22.2 months (9.4-52.7) in group 2 (hazard ratio [HR] 0.87 [0.70-1.10]; p=0.24). Number of patients alive at 5 years was 37 (point estimate 27%) in group 1 and 24 (point estimate 20%) in group 2 (odds ratio 0.63 [0.36-1.10]; p=0.10). With N0 status at thoracotomy, the median OS was 34.4 months (IQR 15.7-not reached; 19 [point estimate 41%] patients alive at 5 years). Progression-free survival (PFS) was better in group 1 than in group 2, median 12.8 months (5.3-42.2) vs 10.5 months (4.8-20.6), HR 0.77 [0.62-0.96]; p=0.017); the number of patients without disease progression at 5 years was 32 (point estimate 22%) versus 13 (point estimate 11%), respectively. Neutropenia and oesophagitis were the main grade 3 or 4 toxicities associated with chemotherapy plus radiotherapy in group 1 (77 [38%] and 20 [10%], respectively) and group 2 (80 [41%] and 44 [23%], respectively). In group 1, 16 (8%) deaths were treatment related versus four (2%) in group 2. In an exploratory analysis, OS was improved for patients who underwent lobectomy, but not pneumonectomy, versus chemotherapy plus radiotherapy., Interpretation: Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patients with stage IIIA(N2) non-small-cell lung cancer., Funding: National Cancer Institute, Canadian Cancer Society, and National Cancer Institute of Canada.

Purposes: This systematic review addressed the following key questions on managing small cell lung cancer (SCLC): the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second-line and subsequent-line treatment for relapsed/progressive disease., Methods: The review methods were defined prospectively in a written protocol. We primarily sought randomized controlled trials that compared the interventions of interest., Results: Robust evidence was lacking for all questions except PCI, for which a patient-level metaanalysis showed that PCI improves survival of SCLC patients who achieved complete response after primary therapy from 15.3 to 20.7% (p = 0.01). The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Metaanalysis did not find significant reductions in 2-year and 3-year mortality rates for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. Relevant comparative studies were nonexistent for management of mixed histology disease and surgery for early limited SCLC. PET may be more sensitive in detecting extracranial disease than conventional staging modalities, but studies were of poor quality., Conclusions: PCI improves survival among those with a complete remission to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components.

Although small-cell lung cancer (SCLC) makes up a smaller proportion of all lung cancers than it did 25 years ago, it remains a common cause of cancer mortality that requires more clinical and basic research than is currently underway. Trials of newer chemotherapy variations have failed to produce a regimen that is clearly superior to the two-drug combination of etoposide and cisplatin, which remains the standard of care for both limited and extensive stage SCLC. Paradoxically, advances in this systemic disease have come from radiotherapy innovations for limited SCLC, including addition of thoracic irradiation to systemic chemotherapy, more intense thoracic irradiation, early integration of thoracic irradiation with systemic chemotherapy, and prophylactic cranial irradiation.

Background: Retrospective analysis of patients with medically inoperable non-small cell lung cancer treated with continuous high-dose external beam radiation therapy at the Medical University of South Carolina., Methods: We identified 35 patients with non-small cell lung cancer treated 1998-2002. None were candidates for resection for reasons including: pulmonary function (n = 23), previous cancer (n = 9), other co-morbidities (n = 2), and refusal of surgery (n = 1). Median percent predicted forced expiratory volume in 1 second was 41.5%. Median age was 71 years. Five patients had more than one primary tumor: three were concurrently treated, two were sequentially treated. Lesion sizes were <3 cm (n = 24); 3-5 cm (n = 12), and >5 cm (n = 5). Nodal stage was as follows: N0 (n = 33) and N1 (n = 2). Radiation therapy was administered once daily: median dose was 80.5 Gy/35 fx/2.3 Gy/fx. The clinical target volume was tumor plus nodes > or =1.0 cm. V20 data were available for 12 patients, with a mean value of 15.7%., Results: Thirty-four patients completed treatment. Median follow-up was 23.0 months. There were 26 deaths: 19 died from non-small cell lung (73%) and seven died from co-morbid illness (27%). Median survival was 24 months (95% CI, 18.0-31.9 months). Four patients were alive with disease, and five were alive disease-free at 10- and 68-month follow-ups. Of 41 lesions, local failure occurred in 15 lesions (37%) of which 3 local failure patients (9%) failed concomitantly in untreated regional lymph nodes. There were no isolated nodal recurrences. Distant progression: 10 patients (29%) of which 6 distant progression without local failure. Two patients who both had prior lobectomies experienced grade 5 toxicities., Conclusion: Continuous high-dose external beam radiation therapy 80.5 Gy administered in 35 fractions was tolerated. Treatment-related death was rare (6%) and isolated to patients with prior lobectomies in an extremely high-risk population. Most mortality was lung cancer-related. The dose of 80.5 Gy in 7 weeks is supported for patients with single lesions and no prior lobectomy. Local failure dominates and higher effective doses should be explored.

Twenty consecutive patients with kidney graft rejection refractory to chemical immunosuppression were treated with local irradiation to the transplanted renal graft (3 x 1.5 Gy). Ten patients were complete responders (median follow-up: 47 months). Six patients were partial responders and failed after 1-4 months. Four patients did not respond.

Small cell lung cancer accounts for less than 20% of all lung cancer. The management of this distinct tumor entity differs from the more common non-small cell lung cancer. Primary prevention of smoking exposure remains the most important public health measure. Although small cell lung is an exquisitely chemosensitive disease it remains ultimately fatal for the great majority of patients. Combination chemotherapy regimens have improved response rate and survival of the last three decades. The combination of cisplatin and etoposide has been considered the standard therapy for over a decade. More intensive triplet combination chemotherapy and high-dose chemotherapy have shown improved response rates and survival. Early concomitant and accelerated radiotherapy improves survival in limited stage disease. This review summarizes the current state of the art and future perspectives in detection, staging and standard therapy of small cell lung cancer. Particular emphasis is given to the importance of concomitant and accelerated radiotherapy and consideration of dose-intensive combination chemotherapy regimens., (Copyright 2004 Elsevier Ireland Ltd.)

Background: Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. STATE-OF-THE-SCIENCE PROCESS: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet. The panel's final statement is available at http://consensus.nih.gov., Conclusions: The panel concluded that the available evidence supports a variety of interventions for treating cancer patients' pain, depression, and fatigue. Clinicians should routinely use brief assessment tools to ask patients about pain, depression, and fatigue and to initiate evidence-based treatments. Assessment should include discussion about common symptoms experienced by cancer patients, and these discussions should continue over the duration of the illness. Impediments to effective symptom management in cancer patients can arise from different sources and interactions among providers, patients and their families, and the health care system. Numerous factors could interfere with adequate symptom management. Among these factors are incomplete effectiveness of some treatments, a lack of sufficient knowledge regarding effective treatment strategies, patient reluctance to report symptoms to caregivers, a belief that such symptoms are simply a part of the cancer experience that must be tolerated, and inadequate coverage and reimbursement for some treatments. Additional research is needed on the definition, occurrence, the treatment of pain, depression, and fatigue, alone and in combination, in adequately funded prospective studies. The panel also concluded that the state of the science in cancer symptom management should be reassessed periodically.

Background: Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. State-of-the-Science Process: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet. The panel's final statement is available at http://consensus.nih.gov., Conclusions: The panel concluded that the available evidence supports a variety of interventions for treating cancer patients' pain, depression, and fatigue. Clinicians should routinely use brief assessment tools to ask patients about pain, depression, and fatigue and to initiate evidence-based treatments. Assessment should include discussion about common symptoms experienced by cancer patients, and these discussions should continue over the duration of the illness. Impediments to effective symptom management in cancer patients can arise from different sources and interactions among providers, patients and their families, and the health care system. Numerous factors could interfere with adequate symptom management. Among these factors are incomplete effectiveness of some treatments, a lack of sufficient knowledge regarding effective treatment strategies, patient reluctance to report symptoms to caregivers, a belief that such symptoms are simply a part of the cancer experience that must be tolerated, and inadequate coverage and reimbursement for some treatments. Additional research is needed on the definition, occurrence, the treatment of pain, depression, and fatigue, alone and in combination, in adequately funded prospective studies. The panel also concluded that the state of the science in cancer symptom management should be reassessed periodically.

Radiotherapy has an expanding role in all phases of treatment of nonsmall cell lung cancer. Evolutions in technique, such as three-dimensional conformal radiotherapy, hold the promise for more effective treatment of patients with early stage disease who are not candidates for surgical intervention. Multimodality therapy for patients with locally advanced disease is evolving rapidly, with evidence accruing as to the optimal schedules and doses of radiotherapy and combination chemotherapy. Palliative dose schedules are being refined that maximize patient comfort while providing substantial symptom relief.

Chemotherapy remains the key treatment for small cell lung cancer; today, that chemotherapy remains cisplatin and etoposide in a variety of acceptable schedules. Attempts to use new drugs in extensive disease have not been as successful as hoped; however, a recent trial from Japan supports the use of irinotecan and cisplatin over the standard cisplatin and etoposide, but these facts need to be verified in western countries. For limited disease, the addition of thoracic radiotherapy for all patients and prophylactic cranial irradiation (PCI) in complete, or near complete, responders have resulted in improved survival. The best results occur with early, intensive thoracic radiotherapy concurrent with chemotherapy and PCI after completion of systemic and local therapy. The use of PCI and thoracic radiotherapy in extensive disease is more controversial and less evidence based. PCI and thoracic radiotherapy may be considered only in patients who have achieved a "systemic" complete response and excellent response in the chest. However, both prospects should be supported if there is complete response systemically and near complete response locally. The role of surgery is of limited value in the unusual cases of mediastinal negative disease, but it is a good treatment for patients with peripheral nodules and sufficient pulmonary function to withstand thoracotomy.

The cytotoxic agent docetaxel not only has proven activity in non-small cell lung cancer-when used alone or in combination-but is also a potent radiosensitizer, and improved treatments are needed in all stages of this disease. In patients with locoregionally advanced (stage III) disease, docetaxel has shown efficacy with manageable toxicities when used alone or in combination with a platinum compound in a sequential manner before localized radical radiotherapy/surgery. Presently, therapeutic gains appear to be maximized by the use of concurrent chemotherapy and irradiation. This review focuses on research with combinations of docetaxel with either cisplatin or carboplatin and radiotherapy. Overall response and survival rates to date provide data worth pursuing. From phase I data, weekly docetaxel at 20 mg/m(2) plus cisplatin at 25 mg/m(2) or carboplatin to an area under the concentration time curve of 2 mg/ml*min with concurrent radiotherapy to 60 Gy over 6 weeks appear to be suitable for phase II trials. Predominant toxicities are esophagitis and neutropenia, but a low frequency of pulmonary toxicity is reported. Induction, concurrent, and consolidation docetaxel-based chemoradiotherapy in potentially resectable disease are all being investigated. Future research could include the investigation of computed tomography/ positron emission tomography-derived target volume radiotherapy, dose-escalated therapy, and alternative fractionation schedules in combination with docetaxel-based cytotoxic chemotherapy.

Purpose: There are no published survival data after chemoradiotherapy (chemoRT) in pathologically documented stage IIIB non-small-cell lung cancer. Studies of radiotherapy (RT) alone or chemotherapy followed by RT yield 5-year survivals less than 10%. The Southwest Oncology Group (SWOG) employed the same concurrent chemoRT induction regimen used in its predecessor trimodality trial to determine the efficacy, safety, and long-term outcome of replacing postinduction surgery with additional chemoRT., Patients and Methods: Eligible patients for SWOG-9019 had pathologic documentation of T4N0/1, T4N2, or N3 stage IIIB non-small-cell lung cancer. They had pulmonary function adequate to withstand combined-modality therapy, identical to the requirements of the previous trial with postchemoRT surgery. Induction therapy was two cycles of cisplatin plus etoposide (PE) concurrent with once-daily thoracic RT (45 Gy). In the absence of progressive disease, RT was completed to 61 Gy, with two additional cycles of cisplatin plus etoposide., Results: Fifty eligible patients were accrued with tumor-node (TN) substage confirmed on central review: 18, T4N0/1; 12, T4N2; and 20, N3. Grade 4 neutropenia was the most common toxicity (32%). Grade 3/4 esophagitis occurred in 12% and 8%. Median follow-up was 52 months, and overall median survival was 15 months (10 to 22, 95% confidence interval). Three- and 5-year survivals were 17% and 15% (5-year T4N0/1, 17%; T4N2, 13%; and N3, 15%)., Conclusion: Feasibility and long-term survival support the application of these results as a standard against which mature outcomes of chemoRT trials with new chemotherapy agents can be compared. These results also justify use of the SWOG-9019 approach as a control arm in ongoing phase III trials.

Purpose: To determine acute and late complications for bladder and rectum and to determine dose-volume correlations., Methods and Materials: Sixty-four patients received definitive treatment for prostate cancer between January 1995 and December 1998 using conformal three-dimensional radiotherapy. Doses ranged from 72 to 80Gy. The acute and late side effects were gathered retrospectively, and graded according to Radiotherapy and Oncology Group criteria (RTOG). The patients were divided into two groups: or=76Gy (Group B) and had a mean follow-up of 32 and 22 months, respectively., Results: No grades 3-4 acute, urinary or rectal toxicity was reported. Acute grade 2 rectal complications were seen in 10 and 18% of the patients in Groups A and B, respectively. They were observed at a mean dose of 38Gy. Acute grade 2 urinary symptoms were 33 and 47% for Groups A and B, respectively. They were seen at a mean dose of 43Gy. Acute rectal symptoms were dose-volume related. Patients without diarrhea had a mean rectal volume receiving a dose of 70Gy or more of 8.5 cm(3). However, patients with RTOG 2 diarrhea had a volume of 16.5 cm(3) (P=0.042). No dose-volume relationship for acute bladder symptoms or late complications were seen. Grades 1-2 late rectal and bladder complications were seen in 11 and 8% of the patients, respectively. None required hospital admission or transfusion., Conclusion: Radiotherapy to the prostate can be given at 80Gy. No grades 3-4 acute, urinary or rectal toxicity was reported. Acute rectal symptoms are dose-volume related.

Purpose: To report the long-term follow-up of Southwest Oncology Group-8269, a phase II North American cooperative group trial of concurrent cisplatin, etoposide, vincristine (PEV), and thoracic radiotherapy (TRT) for limited small-cell lung cancer (L-SCLC)., Methods: 114 eligible patients from 47 institutions enrolled between April, 1985 and March 1986. Patients had documented L-SCLC. Induction chemotherapy consisted of three cycles of PEV. TRT was administered at 1.8 Gy/fraction in 25 daily fractions to a total dose of 45 Gy, to begin concomitantly. Consolidative chemotherapy included two cycles of vincristine, methotrexate, etoposide, doxorubicin and cyclophosphamide. Prophylactic cranial irradiation (PCI) was concurrent with the 3rd cycle of chemotherapy. The PCI dose was 30 Gy in 15 fractions of 2 Gy/fraction., Results: As of May 2000, 5 of 114 remain alive and progression-free with a minimum follow-up interval of 13.2 years, as of May 2000. The median follow-up interval is 14.2 years. Thirty eight patients died of causes other than SCLC and five patients are still alive and progression-free. Of the remaining 71 patients dying of SCLC, local failure (LF) occurred in 24% (17 patients), distant metastasis (DM) occurred in 35% (25 patients), simultaneous LF and DM occurred in 25% (18 patients), and was indeterminate in 16% (11 patients). Thus, LF was a component of failure in 49%. Twenty patients had the CNS as the initial site of failure. Eleven patients (10%) developed fatal second primary cancers, including two with acute myelogenous leukemia, two with squamous cell lung cancer, one each with breast, pancreas, prostate, renal cell, and myelodysplasia. One patient developed both a melanoma and non-Hodgkin's lymphoma., Conclusion: There are long-term survivors with concomitant TRT and PEV. LF and DM are common. Pattern of failure suggests needs to improve local and systemic control.

The treatment of non-small cell lung cancer has continued to evolve with the advent of improved staging technologies, chemotherapeutic agents, and methods of radiation delivery. Treatment of clinically uninvolved, regional lymph nodes historically has been delivered in the attempt to cover unseen disease, reduce regional failure, and improve survival. None of these suppositions has been tested nor are they supported by data. With enhanced staging using modalities like positron emission tomography and esophageal ultrasonography, treatment portals can be designed to encompass known disease with greater accuracy and confidence. Data for early-stage non-small cell lung cancer is now increasing and strongly suggest that eliminating elective nodal irradiation does not result in a high incidence of nodal relapse and does not compromise survival. Three-dimensional conformal radiotherapy incorporates better targeting and beam directions to effect smaller treatment volumes that include only clinically evident disease. It provides treatment techniques that maximize tumor dose and minimize normal tissue toxicity. Using smaller fields that do not incorporate elective nodal regions may allow higher doses, and these may help improve local control and survival in a disease where current results are unacceptable., (Copyright 2000 by W.B. Saunders Company.)

Background: Desmoid tumors (aggressive fibromatoses) are benign neoplasms with high rates of recurrence after surgery. Radiotherapy is sometimes reported to prevent recurrences, but not in all studies. In order to evaluate the effect of radiation, comparative analysis was performed., Methods: The authors conducted a MEDLINE search and collected all articles in the English language on the treatment of "desmoid tumor" or "aggressive fibromatosis" from the years 1983-1998. They categorized treatment into three groups: surgery alone (S), surgery with radiotherapy (S + RT), or radiotherapy alone (RT). The S and S + RT groups were each subdivided according to whether margins were free (-), positive (+), or unknown. Each subgroup was divided into cases with primary, recurrent, or unknown tumor., Results: The local control rates after treatment for cases in the S group with (-) margins, (+) margins, and overall were 72%, 41%, and 61%, respectively. For the S + RT group the local control results were 94%, 75%, and 75%, respectively, significantly different when compared with the results for the S group. For the RT group, the local control was 78%, significantly superior to that of the S group (61%). Cases with primary and recurrent tumors had significantly superior local control rates with S + RT or RT versus S. Radiotherapy complications noted were fibrosis, paresthesias, edema, and fracture., Conclusions: RT or S + RT results in significantly better local control than S. Even after dividing the groups into cases with free and positive margins and cases with primary and recurrent tumors, the best local control is achieved with RT or S + RT., (Copyright 2000 American Cancer Society.)

Background: For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy., Methods: We studied 417 patients with limited small-cell lung cancer. All the patients received four 21-day cycles of cisplatin plus etoposide. We randomly assigned these patients to receive a total of 45 Gy of concurrent thoracic radiotherapy, given either twice daily over a three-week period or once daily over a period of five weeks., Results: Twice-daily treatment beginning with the first cycle of chemotherapy significantly improved survival as compared with concurrent once-daily radiotherapy (P=0.04 by the log-rank test). After a median follow-up of almost 8 years, the median survival was 19 months for the once-daily group and 23 months for the twice-daily group. The survival rates for patients receiving once-daily radiotherapy were 41 percent at two years and 16 percent at five years. For patients receiving twice-daily radiotherapy, the survival rates were 47 percent at two years and 26 percent at five years. Grade 3 esophagitis was significantly more frequent with twice-daily thoracic radiotherapy, occurring in 27 percent of patients, as compared with 11 percent in the once-daily group (P<0.001)., Conclusions: Four cycles of cisplatin plus etoposide and a course of radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results in patients with limited small-cell lung cancer.

Although the need to combine thoracic radiotherapy with systemic chemotherapy in the curative treatment of limited small-cell lung cancer is now widely acknowledged, there is substantial disagreement on how best to do this. This paper reviews radiotherapeutic factors but also highlights the important interactions that occur with some classes of chemotherapeutics. Studies examining variables like dose and volume are clearly in order. Concurrent therapy given early has been adopted throughout most of the world, except Europe. The reasons for this are explored. Multiple studies are now showing excellent results with fewer total cycles of chemotherapy. Integration of newer drugs is another challenge for clinical investigators at the close of this century.

It is now established that the treatment of choice for limited small-cell lung cancer (SCLC) in the United States, Canada, and Japan is thoracic radiotherapy (TRT) combined with etoposide (VePesid), either alone or in conjunction with other agents, especially a platinum agent. The specific factors related to the use of TRT in the treatment of limited SCLC are: (1) dose (total and daily), (2) volume to be irradiated, (3) fractionation, (4) timing of radiation relative to chemotherapy (concurrent, at the same time; alternating, using both within weeks; or sequential, all of one followed by all of the other without any overlap), (5) whether radiation should be given earlier or later in the treatment course, and (6) whether to use a split course (rest intervals during a course of radiotherapy) or a continuous course of radiation. This paper discusses each of these factors.

Radiotherapy is an important component in the treatment of limited stage small cell carcinoma of the lung. It improves both local control and survival. This article reviews the scientific and clinical data that have led to combined therapy being considered the current standard for care of limited stage disease. Questions of radiation dose, treatment volume, fractionation, and integration with chemotherapy are discussed. New avenues of investigation to reduce toxicity and optimize treatment efficacy are also discussed.

Purpose: To assess the feasibility of concurrent chemotherapy and irradiation (chemoRT) followed by surgery in locally advanced non-small-cell lung cancer (NSCLC) in a cooperative group setting, and to estimate response, resection rates, relapse patterns, and survival for stage subsets IIIA(N2) versus IIIB., Patients and Methods: Biopsy proof of either positive N2 nodes (IIIAN2) or of N3 nodes or T4 primary lesions (IIIB) was required. Induction was two cycles of cisplatin and etoposide plus concurrent chest RT to 45 Gy. Resection was attempted if response or stable disease occurred. A chemoRT boost was given if either unresectable disease or positive margins or nodes was found., Results: The median follow-up time for 126 eligible patients [75 stage IIIA(N2) and 51 IIIB] was 2.4 years. The objective response rate to induction was 59%, and 29% were stable. Resectability was 85% for the IIIA(N2) group eligible for surgery and 80% for the IIIB group. Reversible grade 4 toxicity occurred in 13% of patients. There were 13 treatment-related deaths (10%) and 19 others (15%) died of causes not related to toxicity or tumor. Of 65 relapses, 11% were only locoregional and 61% were only distant. There were 26 brain relapses, of which 19 were the sole site or cause of death. There was no survival difference (P = .81) between stage IIIA(N2) versus stage IIIB (median survivals, 13 and 17 months; 2-year survival rates, 37% and 39%; 3-year survival rates, 27% and 24%). The strongest predictor of long-term survival after thoracotomy was absence of tumor in the mediastinal nodes at surgery (median survivals, 30 v 10 months; 3-year survival rates, 44% v 18%; P = .0005)., Conclusion: This trimodality approach was feasible in this Southwest Oncology Group (SWOG) study, with an encouraging 26% 3-year survival rate. An Intergroup study is currently being conducted to determine whether surgery adds more to the risk or to the benefit of chemoRT.

Background: Patients with metastatic or unresectable carcinoma of the esophagus have poor survival, but often require palliation of dysphagia., Methods: Twenty-seven patients with unresectable carcinoma of the esophagus were treated with carboplatin, 5-fluorouracil, and split-course accelerated radiation therapy. Seventy-four percent of patients had adenocarcinoma, and 26% had squamous cell carcinoma., Results: The regimen was well tolerated; 25% of the patients had disease improvement after completing therapy, although the majority of these patients had all of their disease within the radiation field. Ninety-three percent (13/14) of the patients who experienced disease progression during therapy progressed in areas treated with chemotherapy alone. Median survival was 6 months. Fifty-nine percent of the 17 patients who presented with dysphagia achieved durable relief of that symptom., Conclusions: Carboplatin and 5-fluorouracil have low activity in patients with metastatic esophageal cancer. However, in combination with radiation therapy, this regimen is tolerable when the primary goal is palliation of dysphagia near the end of life. Future studies should focus on identifying more active regimens with response and survival as endpoints.

The use of thoracic radiotherapy is important to survival in the treatment of limited disease small-cell lung cancer. How to administer that therapy is the subject of continuing clinical trials and ongoing clinical debates. This article focuses on the issues of fractionation of the radiotherapy and describes the rationale for accelerated treatment and hyperfractionated treatment in small cell lung cancer. Theoretical and clinical concepts and recent trials are discussed. Altered fractionation schemes appear to increase acute responding reactions, but are associated with improved local control. The issue of fractionation and central nervous system tolerance is reviewed. Since the cornerstone therapy for this systematic disease is multiagent chemotherapy, strategies for integration of thoracic radiotherapy and systemic chemotherapy are reviewed. The concepts of sequential, alternating, and concurrent therapy are discussed in the context of clinical trials. The issue of integration in the course of treatment is also discussed. Early versus delayed radiation treatment may have different meanings for clinicians and investigators dealing with this disease. All of these issues are covered for the modern cisplatin-etoposide era.

The treatment of small cell lung cancer is clearly enhanced by the addition of radiation therapy. Survival increases modestly while local thoracic failure as first site of progression is reduced from approximately 60% when chemotherapy alone is used to 30% after combined modality therapy. The variables of radiation dose and treatment volume seem to be important in the successful management of this disease. Local chest control appears to increase as doses are escalated from low levels (25 Gy) to moderate levels (45 to 50 Gy(. With about one third of patients experiencing local chest progression, one can speculate that higher radiation doses might be of value. However, at this time there is no proof that increased dose or dose intensity bears out this promise. Indeed, increasing dose intensity of radiotherapy, eg, twice-daily treatment, increases esophagitis, perhaps reduces local failure, but has not improved overall survival. Using larger total doses or altered fraction schemes must still be considered to be under investigation. To increase dose in a safe manner, reduction in the volume covered by radiation portals will likely need to take place. Modern trials suggest that prophylactic treatment of the radiographically or clinically negative contralateral hilum and/or supraclavicular nodal regions may not be necessary for survival or local control. Importantly, reducing treatment volumes may permit increasing doses without exceding normal tissue tolerance. Also, reduced volumes pave the way for further clinical trials that improve radiation dose delivery by better target definition and more conformal therapy.

The addition of radiotherapy to combination chemotherapy has been shown to improve survival for patients with limited small cell lung cancer (SCLC). Although SCLC is very sensitive to radiotherapy, the impact of radiation may be confounded by interaction among various radiotherapy factors or by the chemotherapeutic agents used in combination. The potential effects of such radiation factors as dose, volume, fractionation, sequence with chemotherapy, and timing (early v late), as well as choice of chemotherapy, therefore must be carefully considered when designing or comparing clinical trials of combined modality therapy for SCLC. The combination of thoracic radiotherapy plus platinum-based chemotherapy currently represents the cornerstone of such combination treatment for SCLC. Many questions remain, however, and it is hoped that new trials will be designed to focus more precisely on unsettled issues.

Although the role of thoracic radiotherapy in limited small cell lung cancer has been established by two meta-analyses, optimization of radiotherapy with chemotherapy requires a full understanding of the chemotherapeutics used and the factors involved in administration of thoracic radiotherapy. The Cisplatin-Etoposide (PE) combination has replaced the cyclophosphamide or doxorubicin as the combination of choice, but it isn't clear whether the addition of the other agents add to benefit or toxicity. New agents continue to be sought to improve systemic failure. This paper focuses on the radiotherapy variables: dose, volume, fractionation, temporal sequencing, and variety of methods of combining the modalities are discussed. Results of a variety of pilot studies using thoracic radiotherapy and the PE combination are discussed. A randomized trial of accelerated radiotherapy versus standard fractionation has been completed within the past year, but results are not yet available. Further trials are warranted to improve integration of modalities in order to increase survival and reduce local and systemic failure without increasing untoward effects.

Purpose: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined., Methods and Materials: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy)., Results: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure., Conclusion: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.

Although systemic failure continues to plague patients receiving combined-modality treatment for limited small-cell lung cancer (SCLC), improvements in chemotherapy, including use of cisplatin/etoposide-based regimens, and radiotherapy have produced increases in median, 2-year, and 5-year survival over the last decade. Employing more conservative volumes of radiotherapy in more aggressive ways, today about 50% of SCLC patients will survive 2 years and 30%, 5 years. Moreover, integrating radiotherapy with chemotherapy early in the course of treatment can potentially eliminate resistant clones. The various factors in radiotherapy, including dose, volume, fractionation, and timing, therefore deserve scrutiny in the reporting and design of clinical trials.

RT has been used routinely in the treatment of NSCLC and SCLC for the past several decades. Although largely considered a palliative treatment by most oncologists, there is increasing evidence that RT, when combined with cisplatin-based chemotherapy or given by altered fractionation, may improve the survival in NSCLC. Three large randomized trials have now shown that RT plus a cisplatin-based combination or cisplatin alone prolongs patient survival. Studies of hyperfractionation and accelerated hyperfractionation have also shown promise and are being tested in randomized trials worldwide. The results from these trials must be assessed against ongoing radiation dose escalation studies using new treatment planning technologies, albeit still in their infancy. These trials are discussed in this report. Systemic therapy is the cornerstone of treatment for SCLC. Although the value of RT was hotly debated during the 1970s and 1980s, it is now well established that RT improves survival when combined with chemotherapy in limited stage patients. Despite this advancement, other issues (such as timing or sequencing of modalities, radiation dose, fractionation, and treatment volume), remain unsettled. Randomized trials designed to address these important issues are in progress.

Recent approaches to the treatment of limited small-cell lung cancer have combined local radiotherapy and systemic chemotherapy in an attempt to improve local control and inhibit distant metastases. Local control is a key indicator of the efficacy of radiotherapy administration in combined-modality regimens. However, even in combined-modality trials using high total radiotherapy doses, local failure rates have ranged from 30 to 50 percent. The components of radiotherapy administration--including dose, volume, fractionation, integration with chemotherapy (concurrent, alternating, or sequential), and timing (early or late administration)--are also important considerations. Hyperfractionation, or the administration of small fractions of radiation more than once daily (usually twice), and accelerated hyperfactionation, or the administration of three fourths of the standard radiation dose two to three times daily, have emerged as important concepts in radiotherapy. Although the optimal chemotherapy regimen for combined-modality treatment has not yet been established, use of cisplatin and etoposide combinations, which do not promote pulmonary, cardiac, or esophageal toxicity, have been particularly appropriate in patients with small-cell lung cancer.

Combined-modality therapy in lung cancer is a common practice throughout the world. The use of radiochemotherapy appears to be firmly established in the treatment of small cell lung cancer, but the role of prophylactic cranial irradiation remains undecided. Many recommend its use in the treatment of non-small cell lung cancer as well, but no facts exist to support this position. Because of poor long-term outcome and high frequency of systemic relapse, integration of chemotherapy for the treatment of non-small cell lung cancer is becoming more prevalent. This article discusses methods of integration, the problems of combined- modality toxicity, recent trials, and reports of multimodal therapy in lung cancer. The advantages of certain regimens of chemotherapy and new methods of radiotherapy are also discussed.

In limited small cell lung cancer (LSCLC), the high local failure rate of chemotherapy by itself (60-100%) and with the addition of external beam radiotherapy (approximately 30%) has led to investigation of methods to improve local control. To that end, we integrated Platinum 60 mg/m2, d. 1, 22 and Etoposide 120 mg/m2, d. 4, 6, & 8; 25, 27 & 29 with concurrent twice-daily 150 cGy (total dose: 4500 cGy). Of 32 consecutively referred patients, 4 with variant histology, 31 were evaluable for toxicity, response, and survival. Two of 4 variant histology patients responded, and 27 of 27 pure small cell responded, p = 0.005. CT scans were inaccurate at forecasting survival. Of 17/32 patients considered "positive," 59% of these were survivors; of those considered "negative," 47% were survivors, p = N.S. Radiation portals were volumetrically conservative; the supraclavicular fossa was included infrequently and the contralateral hilum not at all. Local failure occurred in only 1/27 patients (4%). All four variant patients failed locally, p = 0.001. With a median follow-up of 43 months, the actuarial disease-free survival remains nearly 50%. Variant histology is more predictive of local control than the physical factors of dose or volume.

From 1970 through 1987, 77 patients with Stage I lung cancer were treated with definitive radiation therapy (RT) alone at the Fox Chase Cancer Center or the Hospital of The University of Pennsylvania. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidates for surgical resection because of premorbid medical problems or patient refusal. The median age was 72 years, although 10 patients were over 80. The histologic cell type was squamous in 44, adenocarcinoma in 15, large cell in 3, adenosquamous in 1, non-small cell in 11, and bronchioli-alveolar in 3. Tumor size was retrievable in 75 patients and 25 were less than or equal to 3 cm, 41 from 3-6 cm, and 9 greater than 6 cm. Diagnostic staging varied during the study period. Twelve patients, evaluated with a CT scan of the chest, including the liver, and a bone scan were classified as having "excellent" staging, 24 patients with conventional tomography, liver-spleen scan and a bone scan had "good" staging, and 41 patients were staged less rigorously. The RT was of megavoltage energy in all patients. The median dose was 60 Gy. The mediastinum was treated in all but eight patients who had poor pulmonary function. Survival was measured from the date of pathologic diagnosis. The actuarial 3-year survival rate of the entire group of patients is 17% with a median survival time of 20 months. Of the 61 deaths, 51 were due to disease and 10 were due to intercurrent disease without evidence of tumor recurrence. The actuarial 3-year disease-specific survival (DSS) was 22%. The 3-year disease-specific survival for patients with tumors less than 3 cm and from 3-6 cm was 30% and 17%, respectively. All nine patients with tumors greater than 6 cm were dead of disease. Local progression occurred in 33 patients, resulting in a 44%, 3-year actuarial freedom from local progression. The median time to local failure was 28 months and there were no local failures after 3 years in the 18 patients eligible for observation beyond this point. Of the patients with "excellent" staging, only 2 of 12 were dead of disease compared with 22 of 24 with "good" staging and 30 of 41 of the remainder. In this large group of Stage I non-small cell lung cancer, thorough pre-treatment staging and smaller tumor size are associated with a more favorable outcome.

Granular cell tumor (GCT) is a rare neoplasm traditionally treated with surgical excision alone. However, recurrences and metastases of GCT have been reported. The authors review the literature and report the case of a 33-year-old black woman with a large, recurrent GCT. The patient was treated with adjuvant radiation therapy and followed without evidence of recurrence. Adjuvant radiotherapy may have a role in the treatment of certain GCT thought, by clinical or pathologic criteria, to be at high risk for recurrence or metastasis, especially in those cases where extensive surgical excision would produce unacceptable morbidity.